Cell Biology

Alternative end-joining results in smaller deletions in heterochromatin relative to euchromatin

1. Jacob M. Miller
2. Sydney Prange
3. Huanding Ji
4. Alesandra R. Rau
5. Varandt Y. Khodaverdian
6. Xiao Li
7. Avi Patel
8. Nadejda Butova
9. Avery Lutter
10. Helen Chung
11. Chiara Merigliano
12. Chetan C. Rawal
13. Terrence Hanscom
14. Mitch McVey
15. Irene Chiolo

• Curated by eLife

  eLife assessment

  This manuscript describes valuable new findings on the impact of chromatin context on the outcomes of microhomology-mediated end joining of DNA double-strand breaks (DSBs), specifically a preference for DSB-proximal microhomologies in repair within a heterochromatic compared to a euchromatic locus. The authors develop the Drosophila spermatogonia as a model for repair at induced DSBs in a mitotically-active tissue and leverage this system to provide convincing evidence that the local environment impacts the preference for repair mechanism and outcome. The work could be strengthened by the use of additional euchromatin insertion(s) to robustly validate the findings.

Reviewed by eLife

Ubiquitin ligase and signalling hub MYCBP2 is required for efficient EPHB2 tyrosine kinase receptor function

1. Chao Chang
2. Sara L Banerjee
3. Sung Soon Park
4. Xiao Lei Zhang
5. David Cotnoir-White
6. Karla J Opperman
7. Muriel Desbois
8. Brock Grill
9. Artur Kania

• Curated by eLife

  eLife assessment

  This valuable study identifies an Ephrin type-B Receptor 2 (EPHB2) interactor, MYCBP2, as a potential regulator of EPHB2 stability and function. In contrast to expectations, based on MYCBP2 function in the ubiquitin pathway, loss of function of MYCBP2 resulted in less EPHB2 receptor and defective EPHB2 function. The paper is supported by a largely convincing set of biochemical, cell culture and in vivo experiments.

Reviewed by eLife

Comparative analysis of two Caenorhabditis elegans kinesins KLP-6 and UNC-104 reveals a common and distinct activation mechanism in kinesin-3

1. Tomoki Kita
2. Kyoko Chiba
3. Jiye Wang
4. Atsushi Nakagawa
5. Shinsuke Niwa

• Curated by eLife

  eLife assessment

  This study explores the activation mechanisms of members of the kinesin-3 family, demonstrating common and unique regulation modes with solid evidence. The findings make for valuable contributions to the field of kinesin activation and regulation.

Reviewed by eLife

Atlas of Plasmodium falciparum intraerythrocytic development using expansion microscopy

1. Benjamin Liffner
2. Ana Karla Cepeda Diaz
3. James Blauwkamp
4. David Anaguano
5. Sonja Frolich
6. Vasant Muralidharan
7. Danny W Wilson
8. Jeffrey D Dvorin
9. Sabrina Absalon

• Curated by eLife

  eLife assessment

  This important study provides an unprecedented overview of the subcellular organization of proliferative blood stage malaria parasites using expansion microscopy. The localization of multiple parasite organelles is comprehensively probed using three-dimensional super-resolution microscopy throughout the entire intraerythrocytic development cycle. This work provides a compelling framework to investigate in future more deeply the unconventional cell biology of malaria-causing parasites.

Reviewed by eLife, preLights, Life Science Editors

Trabid patient mutations impede the axonal trafficking of adenomatous polyposis coli to disrupt neurite growth

1. Daniel Frank
2. Maria Bergamasco
3. Michael J Mlodzianoski
4. Andrew Kueh
5. Ellen Tsui
6. Cathrine Hall
7. Georgios Kastrappis
8. Anne Kathrin Voss
9. Catriona McLean
10. Maree Faux
11. Kelly L Rogers
12. Bang Tran
13. Elizabeth Vincan
14. David Komander
15. Grant Dewson
16. Hoanh Tran

• Curated by eLife

  eLife assessment

  This study defines the roles for two different missense mutations observed in patients in the Trabid/ZRANB1 gene associated in children with a range of congenital disorders including reduced brain size. The study is important because the findings have theoretical or practical implications beyond a single subfield, as the study of DUB and cytoskeletal alterations have implications for neurodevelopment broadly. The methods are convincing as they utilize appropriate and validated methodology in line with current state-of-the-art by incorporating knock-in mice of the patient mutations. Many of the reviewer comments were focused on potential next experiments, rather than on evaluation of the data at hand, and the authors have considered these as future studies. The work as presented suggests critical roles for Trabid in the STRIPAK complex mediating APC deubiquitylation.

Reviewed by eLife

Heterogeneous non-canonical nucleosomes predominate in yeast cells in situ

1. Zhi Yang Tan
2. Shujun Cai
3. Alex J Noble
4. Jon K Chen
5. Jian Shi
6. Lu Gan

• Curated by eLife

  eLife assessment

  This important paper exploits new cryo-EM tomography tools to examine the state of chromatin in situ. The experimental work is meticulously performed, with a vast amount of data collected, with convincing interpretation of possible nucleosomal structures in yeast. The majority of these nucleosomes appear not to possess stable octameric configurations. Although it cannot be excluded that there could be an unknown bias in class detection, we agree that the authors have gone as far as is possible, given constraints in current technology and analysis, to support their model. Despite the provocative nature of this report, it is our hope that such work will spark debate, and further the development of exciting new tools that can interrogate the dynamic nature of the nucleosome, and its associated functions in situ.

Reviewed by eLife

Pharmacological inhibition of CLK2 activates YAP by promoting alternative splicing of AMOTL2

1. Maya L Bulos
2. Edyta M Grzelak
3. Chloris Li-Ma
4. Emily Chen
5. Mitchell Hull
6. Kristen A Johnson
7. Michael J Bollong

• Curated by eLife

  eLife assessment

  This paper reports important findings on a potent activator of the YAP pathway, demonstrating its mechanism through alternative splicing changes. The authors provide convincing evidence to support their claims. This research is of interest to biologists studying alternative splicing or the Hippo pathway, with significant implications for medical research.

Reviewed by eLife

Palmitoylation of proteolipid protein M6 promotes tricellular junction assembly in epithelia of Drosophila

1. Raphael Schleutker
2. Stefan Luschnig

Reviewed by Review Commons

Mitochondrial electron transport chain, ceramide, and coenzyme Q are linked in a pathway that drives insulin resistance in skeletal muscle

1. Alexis Diaz-Vegas
2. Søren Madsen
3. Kristen C Cooke
4. Luke Carroll
5. Jasmine XY Khor
6. Nigel Turner
7. Xin Y Lim
8. Miro A Astore
9. Jonathan C Morris
10. Anthony S Don
11. Amanda Garfield
12. Simona Zarini
13. Karin A Zemski Berry
14. Andrew P Ryan
15. Bryan C Bergman
16. Joseph T Brozinick
17. David E James
18. James G Burchfield

• Curated by eLife

  eLife assessment

  This important study highlights a potential connection between fatty acid intrusion into myocytes and increases in mitochondrial ceramide that cause deficits in coenzyme Q and consequent insulin resistance. The authors primarily use the L6 myocyte model, which may not fully recapitulate in vivo conditions, however, the manuscript shows compelling data in mice that substantially supports the L6 cell results. Overall, this study provides a strong framework for a compelling pathway of myocyte dysfunction and for continued efforts to test the important hypotheses that are presented.

Reviewed by eLife

LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility

1. Jae Yeon Hwang
2. Pengxin Chai
3. Shoaib Nawaz
4. Jungmin Choi
5. Francesc Lopez-Giraldez
6. Shabir Hussain
7. Kaya Bilguvar
8. Shrikant Mane
9. Richard P Lifton
10. Wasim Ahmad
11. Kai Zhang
12. Jean-Ju Chung

• Curated by eLife

  eLife assessment

  This study provides valuable findings on a causative relationship between LRRC23 mutations and male infertility due to asthenozoospermia. The evidence supporting the conclusions is solid. This work will be of interest to biomedical researchers who work on sperm biology and non-hormonal male contraceptive development.

Reviewed by eLife